Development of Heteroatom-Centered Radical Approaches to Hydrocarbon Functionalization

Schmidt, Valerie Anne

Development of Heteroatom-Centered Radical Approaches to Hydrocarbon Functionalization

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March 19, 2019

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Schmidt, Valerie Anne
- Affiliation: College of Arts and Sciences, Department of Chemistry

Abstract

I.Alkene Difunctionalizations An overview of alkene difunctionalization reactions is presented. The current landscape of alkene dioxygenations, oxyaminations, and diaminations is discussed. II.Aerobic Intramolecular Alkene Dioxygenations Using Hydroxamic Acids In the presence of either oxygen or air as the sole oxidant and external oxygen-atom source, a variety of unsaturated hydroxamic acids afford cyclic hydroxamates that are readily converted into 1,2-diols, with the potential for high levels of reaction stereocontrol. III.Aerobic Intermolecular Alkene Dioxygenations Using Hydroxamic Acids The dioxygenation of alkenes using molecular oxygen and a simple hydroxamic acid derivative is described. The reaction system consists of readily prepared methyl N-hydroxy-N-phenylcarbamate and molecular oxygen with a radical initiator, offering an alternative to common dioxygenation processes catalyzed by precious transition metals. This transformation capitalizes on the unique reactivity profile of hydroxamic acid derivatives in radial-mediated alkene addition processes. IV.Aerobic Alkene Ketooxygenations Using Hydroxamic Acids A radical-mediated alkene ketooxygenation is described. This four-electron alkene oxidation delivers alpha-oxyketones directly from simple alkenes with high levels of regio- and stereocontrol. V.Radical-Mediated Alkene Oxyaminations Using Hydroxamic Acids A radical-mediated approach to alkene oxyamination is described. This method capitalizes on the unique reactivity of the amidoxyl radical in alkene additions to furnish a general difunctionalization using simple diisopropyl azodicarboxylate (DIAD) as a radical trap. The intramolecular nature of the process provides single regioisomer products in all cases. Difunctionalizations of cyclic alkenes provide trans oxyamination products inaccessible using current methods with high levels of stereoselectivity, complementing cis-selective oxyamination processes. VI.Radical-Mediated Alkene Carbooxygenations Using Hydroxamic Acids A radical-mediated approach to alkene carbooxygenation using hydroxamic acids is described. These transformations represent rare examples of direct carbooxygenations, and deliver versatile functionality to the unsaturated substrate. Included in this study are alkene oxyallylation, oxycyanation, and formal oxyacylation processes. VII.Heteroatom-Centered Radical Aliphatic C-H Halogenations A site-selective approach to C-H halogenation using nitrogen-centered radicals is outlined. Developing predictably selective C-H functionalizations has the potential to revolutionize the way chemists construct molecules. Nitrogen-centered radicals have demonstrated promising steric and electronic selectivity in the bromination of alkane substrates under neutral conditions. Initial functionalization studies of complex molecules are also described.

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